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Sodium Carbonate → (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

HRID 718339
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HRID 718339 반응식
Br[C:2]1[C:3]([N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[C:4]([C@H:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8].[F:29][C:30]1[CH:46]=[CH:45][C:33]([CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=2)=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:17]([O:16][C@@H:10]([C:4]1[C:5]([CH3:9])=[N:6][C:7]([CH3:8])=[C:2]([C:39]2[CH:38]=[CH:37][C:36]([O:35][CH2:34][C:33]3[CH:32]=[CH:31][C:30]([F:29])=[CH:46][CH:45]=3)=[CH:41][CH:40]=2)[C:3]=1[N:21]1[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]1)[C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH3:20])([CH3:19])[CH3:18]
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 16218069B-(4-((4-Fluorophenyl)methoxy)phenyl)boronic acidHCID 118314215Ethyl (S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

생성물 1

HCID 118314204(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate수율 60.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매
HCID 6228Dimethylformamide용매

실험 절차

A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.049 g, 0.108 mmol), (4-((4-fluorobenzyl)oxy)phenyl)boronic acid (0.040 g, 0.161 mmol) and 2M Na2CO3 (0.134 ml, 0.269 mmol) in DMF (2 mL) was degassed for 10 min. Then, Pd(Ph3P)4 (0.012 g, 10.76 μmol) was added, degassed for 5 min and placed in a pre-heated oil bath at 100° C. After 1.5 h at 110° C., cooled and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0372 g, 0.065 mmol, 59.9% yield) as tan color solid. LCMS (M+H)=577.6.

후처리

  1. customwas degassed for 10 min
  2. customdegassed for 5 min
  3. customplaced in a pre-heated oil bath at 100° C
  4. temperaturecooled
  5. custompurified by prep-HPLC

출처 및 근거

ORD 기록
ord-cefc071cfc2e4456b1d97021ab7da709
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09193720B2

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